The present invention relates to new medicaments for topical use and more precisely it concerns medicaments containing:
1. an active pharmacological substance or a mixture of pharmacological substances, either active or suitable for topical administration and
2. a vehicle which comprises hyaluronic acid or a molecular fraction of hyaluronic acid or a salt of the same with an alkaline metal, an alkaline earth metal, magnesium, aluminium, ammonium or a pharmacological substance, optionally together with additional conventional excipients for pharmaceutical preparations for topical use. The invention further relates to the use of such medicaments for therapeutic or preventive purposes.
The application of a topically active medicament may be a benefit or remedy, especially in dermatology, diseases of the mucuous membranes in general and particularly membranes of the oral and nasal cavities, diseases of the outer ear, and especially diseases of the outer surface of the eye. Application of these topical medicaments is particularly advisable in pediatrics and in the veterinary field.
The advantages of therapy using the medicaments according to the present invention are due to a more efficient vehicle for the drugs promoted by the acidic polysaccharide of the hyaluronic acid component and to a better bioavailability of the active substance as compared to that obtainable with known pharmaceutical formulations. Furthermore, the new medicaments of the invention assume particular importance in the case of ophthalmic medicaments, because due to the above mentioned qualities, there is an additional special compatibility with the corneal epithelium and, therefore, a very high level of tolerability, with no sensitization effects. When the medicaments are administered in the form of concentrated solutions with elastic-viscose characteristics or in solid form, it is possible to obtain films on the corneal epithelium which are homogeneous, stable, perfectly transparent, and which adhere well, quaranteeing prolonged bioavailability of the drug, thereby forming excellent preparations with a retard effect.
Such ophthalmic medicaments are of exceptional value especially in the veterinary field, considering for example that there are at present no veterinary specialities for oculistic use containing chemotherapeutics. Indeed, preparations intended for human use are usually used, and these do not always guarantee a specific range of activity nor comply with the particular conditions in which the treatment should be effected.
This is the case, for example, in therapy for infectious keratoconjunctivitis, pink eye or IBK, an infection which mainly affects cattle, sheep and goats. Presumably, these three species have in common specific etiological factors. In particular, in cattle the main microorganism involved seems to be Moraxella bovis (even though other agents of a viral origin should not be excluded, such as Rhinotracheitis virus, Micoplasma, Rickettsia and Chlamydia in the case of sheep, and Rickettsia in the case of goats). The disease manifests itself in an acute form and tends to spread quickly. In the initial stages the symptomatology is characterized by blepharospasm and excessive lacrimation, followed by purulent exudate, conjuctivitis and keratitis, often accompanied by fever, reduced apetite and milk production. Lesions of the cornea are particularly serious and in the final stages can even cause perforations of the cornea itself. The clinical course varies from a few days to several weeks.
A vast range of chemotherapeutic agents are used for treatment, administered both topically (often in association with anti-inflammatory steroids), and systemically. Among these are the following: tetracyclines, such as oxytetracycline, penicillins, such as cloxacillin and benzylpenicillin, sulfamides, polymyxin B (associated with miconazole and prednisolone), chloramphenicol, tylosin and chloromycetin. Topical treatment of the disease, despite its apparent simplicity, still represents an unsolved problem, since for one reason or another it has proved impossible up until now to obtain oculistic preparations having concentrations of antibiotics or sulfamides which are therapeutically effective in the secretion of tears. This is quite understandable in the case of solutions, bearing in mind the mainly reclining position of the head in these animals. But it is also true of semisolid medicaments, since the excipients normally used in them do not have the qualities necessary for adhering to the surface of the cornea, as they do not usually have a sufficiently high concentration of active substance and cannot achieve perfect distribution (i.e., the presence of a distribution gradient). These defects of conventional colliriums in ophthalmic use have been described by Slatter et al. in "Austr. vet. J.," 1982, 59 (3), pp. 66-72.